tbuckley/cabot-search huggingface dataset:
RNF157 attenuates CD4<sup>+</sup> T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation
Authors: Peng Wang, Jingjing Zhao, Yunke Tan, Junli Sheng, Shitong He, Yitian Chen, Dingnai Nie, Xiaolong You, Jinmei Luo, Yanling Zhang, Shengfeng Hu
Journal: Theranostics (2023)

Background: CD4 + T cells play an important role in body development and homeostasis.Quantitative and functional changes in CD4 + T cells result in abnormal immune responses, which lead to inflammation, cancer, or autoimmune diseases, such as multiple sclerosis (MS).Ubiquitination plays an essential role in the differentiation and functioning of CD4 + T cells.However, the function of several E3 ubiquitin ligases in CD4 + T cell differentiation and T cell-mediated pathological diseases remains unclear.Methods: RNA sequencing data were analyzed to identify the E3 ubiquitin ligases that participate in the pathogenesis of MS.Furthermore, conditional knockout mice were generated.Specifically, flow cytometry, qPCR, western blot, CO-IP and cell transfer adoptive experiments were performed.Results: In this study, we identified The RING finger 157 (RNF157) as a vital regulator of CD4 + T cell differentiation; it promoted Th1 differentiation but attenuated Th17 differentiation and CCR4 and CXCR3 expressions in CD4 + T cells, thereby limiting experimental autoimmune encephalomyelitis development.Mechanistically, RNF157 in CD4 + T cells targeted HDAC1 for K48-linked ubiquitination and degradation.Notably, RNF157 expression was significantly decreased and showed a significant negative correlation with RORγt expression in patients with MS. Conclusions:Our study highlights the critical role of RNF157 in regulating CD4 + T cell functions in autoimmune diseases and suggests RNF157 as a potential target in adaptive immune responses against MS and other autoimmune disorders.
Curcumin-zinc framework encapsulated microneedle patch for promoting hair growth
Authors: Yating Yang, Pei Wang, Yan Gong, Ziyou Yu, Yuci Gan, Peizhe Li, Wei Liu, Xiansong Wang
Journal: Theranostics (2023)

Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications.Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect.Method: We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system.ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD).The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM.The in vitro ZnMOF release profile and the in vivo penetration of ZnMOF-MN were also evaluated.The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs).Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing in vivo.Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining.Results: ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm.ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn 2+ and curcumin.In vitro, ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency.In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration.Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models.Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. Conclusion:The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.
LncRNAs associated with oxidative stress in diabetic wound healing: Regulatory mechanisms and application prospects
Authors: Qinzhi Yang, Dan Fang, Jinxiang Chen, Shaorun Hu, Ni chen, Jun Jiang, Min Zeng, Mao Luo
Journal: Theranostics (2023)

Diabetes is a group of chronic diseases with blood glucose imbalance, and long-term hyperglycaemia causes sustained damage to various organs of the body, resulting in vascular lesions, neuropathy and impaired wound healing.Diabetic wound formation involves a variety of complex mechanisms, and they are characterized by a persistent chronic inflammatory response, degradation of angiogenesis and imbalance of extracellular matrix regulation, all of which are related to oxidative stress.Additionally, repair and healing of diabetic wounds require the participation of a variety of cells, cytokines, genes, and other factors, which together constitute a complex biological regulatory network.Recent studies have shown that long noncoding RNAs (lncRNAs) can be involved in the regulation of several key biological pathways and cellular functions demonstrating their critical role in diabetic wound healing.LncRNAs are a major family of RNAs with limited or no protein-coding function.Numerous studies have recently reported a strong link between oxidative stress and lncRNAs.Given that both lncRNAs and oxidative stress have been identified as potential drivers of diabetic wound healing, their link in diabetic wound healing can be inferred.However, the specific mechanism of oxidative stress related to lncRNAs in diabetic wound healing is still unclear, and elucidating the functions of lncRNAs in these processes remains a major challenge.This article reviews the mechanisms of lncRNAs related to oxidative stress in several stages of diabetic wound healing and discusses diagnostic and treatment potential of lncRNAs to treat diabetic wounds by improving oxidative stress, as well as the challenges of using lncRNAs for this purpose.It is hoped that these results will provide new targets and strategies for the diagnosis and treatment of impaired wound healing in diabetic patients.
Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling: Erratum
Authors: Ping Ji, Yongxin Zhou, Yibao Yang, Junlu Wu, Hao Zhou, Wenqiang Quan, Junjun Sun, Yiwen Yao, Anquan Shang, Chenzheng Gu, Bingjie Zeng, Jenni Firrman, Weidong Xiao, Robert Bals, Zujun Sun, Dong Li
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.30726.].
A <i>de novo</i> dual-targeting supramolecular self-assembly peptide against pulmonary metastasis of melanoma
Authors: Jingjing Wang, Xiaoqiang Zheng, Xiao Fu, Aimin Jiang, Yu Yao, Wangxiao He
Journal: Theranostics (2023)

Despite recent advances in treatment, overall survival rates for metastatic melanoma, especially those that invade the lungs, continue to be low, with 5-year survival rates of only 3% to 5%. It was recently discovered that Wnt/β-catenin signaling pathways and MAPK/ERK signaling pathways are involved in melanoma metastasis.
Label-free optical metabolic imaging of adipose tissues for prediabetes diagnosis
Authors: Liping Chen, Guihui Qin, Yuhong Liu, Moxin Li, Yue Li, Lun-Zhang Guo, Lidong Du, Weiming Zheng, Pei-Chun Wu, Yueh-Hsun Chuang, Xiaoyan Wang, Tzung-Dau Wang, Ja-An Annie Ho, Tzu-Ming Liu
Journal: Theranostics (2023)

Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology.
Bispecific antibodies targeting EGFR/Notch enhance the response to talazoparib by decreasing tumour-initiating cell frequency
Authors: Wenyan Fu, Guangyao Li, Changhai Lei, Kewen Qian, Shuyi Zhang, Jian Zhao, Shi Hu
Journal: Theranostics (2023)

Poly ADP ribose polymerase (PARP) inhibitors are mainly used in treating BRCA-mutant cancers, and their application in novel therapies to expand their benefit is of interest in personalized medicine.A recent report showed that pharmacological targeting of PARP increases the sensitivity of cancer cells to EGFR inhibition, but the therapeutic value of this combination has not been fully determined.We propose a strategy of combining PARP inhibitors with bispecific antibodies that target both EGFR and Notch signalling, highlighting the difficulties posed by deregulation of Notch signalling and the enrichment of cancer stem cells (CSCs) during therapy.In the present study, we showed that although PARP plus EGFR targeting led to more penetrant and durable responses in the non-small cell lung cancer (NSCLC) PDX model, it influenced the enrichment of stem-like cells and their relative proportion.Stem-like cells were significantly inhibited in vitro and in vivo by EGFR/Notch-targeting bispecific antibodies.These bispecific antibodies were effective in PDX models and showed promise in cell line models of NSCLC, where they delayed the development of acquired resistance to cetuximab and talazoparib.Moreover, combining EGFR/Notch-targeting bispecific antibodies and talazoparib had a more substantial antitumour effect than the combination of talazoparib and cetuximab in a broad spectrum of epithelial tumours.EGFR/Notch bispecific antibodies decrease the subpopulation of stem-like cells, reduce the frequency of tumour-initiating cells, and downregulate mesenchymal gene expression.These findings suggest that combining EGFR and Notch signalling blockade can potentially increase the response to PARP blockade.
Environmentally sensitive photosensitizers enable targeted photodynamic ablation of Gram-positive antibiotic resistant bacteria
Authors: Sam Benson, Alex Kiang, Charles Lochenie, Navita Lal, Syam Mohan P. C. Mohanan, Gareth O. S. Williams, Kevin Dhaliwal, Bethany Mills, Marc Vendrell
Journal: Theranostics (2023)

Bacterial infections remain among the biggest challenges to human health, leading to high antibiotic usage, morbidity, hospitalizations, and accounting for approximately 8 million deaths worldwide every year.The overuse of antibiotics and paucity of antimicrobial innovation has led to antimicrobial resistant pathogens that threaten to reverse key advances of modern medicine.Photodynamic therapeutics can kill bacteria but there are few agents that can ablate pathogens with minimal off-target effects.Methods: We describe nitrobenzoselenadiazoles as some of the first environmentally sensitive organic photosensitizers, and their adaptation to produce theranostics with optical detection and light-controlled antimicrobial activity.We combined nitrobenzoselenadiazoles with bacteria-targeting moieties (i.e., glucose-6-phosphate, amoxicillin, vancomycin) producing environmentally sensitive photodynamic agents.Results: The labelled vancomycin conjugate was able to both visualize and eradicate multidrug resistant Gram-positive ESKAPE pathogens at nanomolar concentrations, including clinical isolates and those that form biofilms.Conclusion: Nitrobenzoselenadiazole conjugates are easily synthesized and display strong environment dependent ROS production.Due to their small size and non-invasive character, they unobtrusively label antimicrobial targeting moieties.We envisage that the simplicity and modularity of this chemical strategy will accelerate the rational design of new antimicrobial therapies for refractory bacterial infections.
Therapeutic silencing of lncRNA RMST alleviates cardiac fibrosis and improves heart function after myocardial infarction in mice and swine
Authors: Teng Ma, Fan Qiu, Yanshan Gong, Hao Cao, Gonghua Dai, Daohan Sun, Dongling Zhu, Han Lei, Zhongmin Liu, Ling Gao
Journal: Theranostics (2023)

Rationale: Cardiac fibrosis is an adverse consequence of aberrant fibroblast activation and extracellular matrix (ECM) deposition following myocardial infarction (MI).Recently, long noncoding RNAs (lncRNAs) have been reported to participate in multiple cardiac diseases.However, the biological functions of lncRNA rhabdomyosarcoma 2-associated transcript (RMST) in cardiac fibrosis remain largely unknown.Methods: The role of RMST in regulating cardiac fibroblast (CF) proliferation, fibroblast-to-myofibroblast transition (FMT), and ECM production, which were induced by transforming growth factor-β1, was evaluated through immunofluorescence staining, cell contraction assay, cell migration assay, qRT-PCR, and western blot.The therapeutic effect of RMST silencing was assessed in murine and porcine MI models.Results: The present study showed that RMST expression was upregulated and associated with cardiac fibrosis in murine and porcine MI models.Further loss-of-function studies demonstrated that RMST silencing in vitro significantly inhibited CF proliferation, FMT, and ECM production.Accordingly, RMST knockdown in vivo alleviated cardiac fibrosis and improved cardiac contractile function in MI mice.Moreover, RMST acted as a competitive endogenous RNA of miR-24-3p.miR-24-3p inhibition abolished, while miR-24-3p agomir reproduced, the RMST knockdown-mediated effects on CF fibrosis by regulating the lysyl oxidase signaling pathway.Finally, the therapeutic potential of RMST knockdown was evaluated in a porcine MI model, and local RMST knockdown significantly inhibited cardiac fibrosis and improved myocardial contractile function in pigs after MI.Conclusion: Our findings identified RMST as a crucial regulator of cardiac fibrosis, and targeting RMST may develop a novel and efficient therapeutic strategy for treating fibrosis-related cardiac diseases.
A systematic review of ultrasound-mediated drug delivery to the eye and critical insights to facilitate a timely path to the clinic
Authors: Isaac J Rad, Luke Chapman, Karnaker Reddy Tupally, Martin Veidt, Hussain Al-Sadiq, Robert Sullivan, Harendra S Parekh
Journal: Theranostics (2023)

Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications.Yet, with 20 years of learnings behind us, clinical translation remains limited.To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both ex vivo and in vivo models.The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments.Methods: In this review, we reflected on study quality of reporting, and risk of bias (RoB) using the latest Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines, alongside the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tools.Literature studies from 2002 to 2022 were initially characterised according to methods of ultrasound application, ultrasound parameters applied, animal models employed, as well as safety and efficacy assessments.This exercise contributed to developing a comprehensive understanding of the current state of play within ultrasound-mediated ocular drug delivery.The results were then synthesised and processed into a guide to aid future study design, with the goal of improving the reliability of data, and to support efficient and timely translation to the clinic.Results: Key attributes identified as hindering translation included: poor reporting quality and high RoB, skewed use of animals unrepresentative of the human eye, and the over reliance of reductionist safety assessments.Ex vivo modelling studies were often unable to have comprehensive safety assessments performed on them, which are imperative to determining treatment safety, and represent a pre-requisite for clinical translation. Conclusion:With the use of our synthesised guide, and a thorough understanding of the underlying physicochemical interactions between ultrasound and ocular biology provided herein, this review offers a firm foundation on which future studies should ideally be built, such that ultrasound-mediated ocular drug delivery can be translated from concept to the coalface where it can provide immense clinical benefit.
Senescent melanocytes driven by glycolytic changes are characterized by melanosome transport dysfunction
Authors: Young Joon Park, Jin Cheol Kim, Yeongeun Kim, Yul Hee Kim, Soon Sang Park, Charlotte Muther, Agnès Tessier, Gimyung Lee, Gaëlle Gendronneau, Sandra Forestier, Youcef Ben-Khalifa, Tae Jun Park, Hee Young Kang
Journal: Theranostics (2023)

Rationale: Senescent melanocytes accumulate in photoaged skin and are closely related to skin aging. A better understanding of the molecular characteristics of senescent melanocytes may be the key to controlling skin aging. Methods: We have developed an in vitro model of senescence in melanocytes using UV irradiation and investigated the functional characteristics and molecular mechanisms underlying senescence in UV-irradiated melanocytes. Results: We have highlighted that in vitro senescent melanocytes are characterized by melanosome transport dysfunction resulting in melanin accumulation. The defective melanosome transport was confirmed with the ultrastructural characterization of both in vitro UV-induced senescent melanocytes and in vivo melanocytes of hypopigmented aging skin. A single-cell transcriptomic analysis revealed that the glycolytic metabolism pathway appeared to be significantly upregulated in most senescent phenotypes. Furthermore, the inhibition of glycolysis by pharmacological compounds mitigates the pro-aging effects of melanocytes senescence, suggesting that alterations in cellular glucose metabolism act as a driving force for senescence in melanocytes. Conclusion: These results demonstrate that senescent melanocytes are characterized by glycolytic metabolism changes and a defective melanosome transport process, which may be related to impaired mitochondrial function, highlighting the importance of metabolic reprogramming in regulating melanocyte senescence.
Intrinsic mechanism and pharmacologic treatments of noise-induced hearing loss
Authors: Ke Xu, Baoying Xu, Jiayi Gu, Xueling Wang, Dehong Yu, Yu Chen
Journal: Theranostics (2023)

Noise accounts for one-third of hearing loss worldwide.Regretfully, noise-induced hearing loss (NIHL) is deemed to be irreversible due to the elusive pathogenic mechanisms that have not been fully elucidated.The complex interaction between genetic and environmental factors, which influences numerous downstream molecular and cellular events, contributes to the NIHL.In clinical settings, there are no effective therapeutic drugs other than steroids, which are the only treatment option for patients with NIHL.Therefore, the need for treatment of NIHL that is currently unmet, along with recent progress in our understanding of the underlying regulatory mechanisms, has led to a lot of new literatures focusing on this therapeutic field.The emergence of novel technologies that modify local drug delivery to the inner ear has led to the development of promising therapeutic approaches, which are currently under clinical investigation.In this comprehensive review, we focus on outlining and analyzing the basics and potential therapeutics of NIHL, as well as the application of biomaterials and nanomedicines in inner ear drug delivery.The objective of this review is to provide an incentive for NIHL's fundamental research and future clinical translation.
Platelet membrane-coated alterbrassicene A nanoparticle inhibits calcification of the aortic valve by suppressing phosphorylation P65 NF-κB
Authors: Bingchuan Geng, Xing Chen, Jiangyang Chi, Fengli Li, Wai Yen Yim, Kan Wang, Chenghao Li, Minghui Xie, Peng Zhu, Zhengfeng Fan, Jiawei Shi, Zhengxi Hu, Yonghui Zhang, Nianguo Dong
Journal: Theranostics (2023)

Rationale: Calcific aortic valve disease (CAVD) is a leading cause of cardiovascular mortality and morbidity with increasing prevalence and incidence.The pathobiology of CAVD involves valvular fibrocalcification, and osteogenic and fibrogenic activities are elevated in aortic valve interstitial cells (VICs) from diseased valves.It has been demonstrated that activated NF-κB pathway was present in the early stage of CAVD process.There is currently no effective clinical drugs targeting NF-κB pathway for CAVD treatment.Therefore, it is of great clinical significance to seek effective treatments for valve calcification.Methods: In this study, we established immortal human valve interstitial cells (im-hVICs) with pGMLV-SV40T-puro lentivirus.Alizarin red staining and western blotting were performed to evaluate the calcification of immortal VICs supplemented with different compounds.The natural fusicoccane diterpenoid alterbrassicene A (ABA) was found to have potential therapeutic functions.Ribonucleic acid sequencing was used to identify the potential target of ABA.Platelet membrane-coated nanoparticle of ABA (PNP-ABA) was fabricated and the IBIDI pump was used to evaluate the adhesion ability of PNP-ABA.Murine wire-induced aortic valve stenosis model was conducted for in vivo study of PNP-ABA.Results: The natural fusicoccane diterpenoid ABA was found to significantly reduce the calcification of human VICs during osteogenic induction via inhibiting the phosphorylation P65.Runt-related transcription factor 2 (Runx2) and bone morphogenetic protein-2 (BMP2) were down regulated with the treatment of ABA in human VICs.Additionally, molecular docking results revealed that ABA bound to RelA (P65) protein.Phosphorylation of P65 (Ser536) was alleviated by ABA treatment, as well as the nuclear translocation of P65 during osteogenic induction in human VICs.Alizarin red staining showed that ABA inhibited osteogenic differentiation of VICs in a dose-dependent manner.PNP-ABA attenuated aortic valve calcification in murine wire-induced aortic valve stenosis model in vivo. Conclusions:The establishment of im-hVICs provides a convenient cell line for the study of CAVD.Moreover, our current research highlights a novel natural compound, ABA, as a promising candidate to prevent the progression of CAVD.